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Experimental Eye Research Apr 2022Glaucoma, a degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Currently, there is no curative treatment. The only proven... (Review)
Review
Glaucoma, a degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Currently, there is no curative treatment. The only proven treatment is lowering intraocular pressure (IOP), the most important risk factor. Glaucoma filtration surgery (GFS) can effectively lower IOP. However, approximately 10% of all surgeries fail yearly due to excessive wound healing, leading to fibrosis. GFS animal models are commonly used for the development of novel treatment modalities. The aim of the present review was to provide an overview of available animal models and anti-fibrotic drug candidates. MEDLINE and Embase were systematically searched. Manuscripts until September 1st 2021 were included. Studies that used animal models of GFS were included in this review. Additionally, the snowball method was used to identify other publications which had not been identified through the systematic search. Two hundred articles were included in this manuscript. Small rodents (e.g. mice and rats) are often used to study the fibrotic response after GFS and to test drug candidates. Due to their larger eyes, rabbits are better suited to develop medical devices. Novel drugs aim to inhibit specific pathways, e.g. through the use of modulators, monoclonal antibodies, aqueous suppressants or gene therapy. Although most newly studied drugs offer a higher safety profile compared to antimetabolites, their efficacy is in most cases lower when compared to MMC. Current literature on animal models and potential drug candidates for GFS were summarized in this review. Future research should focus on refining current animal models (for example through the induction of glaucoma prior to undertaking GFS) and standardizing animal research to ensure a higher reproducibility and reliability across different research groups. Lastly, novel therapies need to be further optimized, e.g. by conducting more research on the dosage, administration route, application frequency, the option of creating combination therapies, or the development of drug delivery systems for sustained release of anti-fibrotic medication.
Topics: Animals; Fibrosis; Filtering Surgery; Glaucoma; Intraocular Pressure; Mice; Mitomycin; Models, Animal; Pharmaceutical Preparations; Rabbits; Rats; Reproducibility of Results
PubMed: 35114212
DOI: 10.1016/j.exer.2022.108972 -
Urologic Oncology Apr 2023Non-muscle invasive bladder cancer (NMIBC) is characterized by a high rate of recurrence and progression, despite surgery and adjuvant therapies. (Review)
Review
BACKGROUND
Non-muscle invasive bladder cancer (NMIBC) is characterized by a high rate of recurrence and progression, despite surgery and adjuvant therapies.
OBJECTIVE
To analyze the published results on the effectiveness of mitomycin C (MMC) applied with an electromotive drug administration device (EMDA) in the treatment of patients with non-muscle invasive bladder tumors.
METHOD
A systematic review was conducted using the PubMed and Google Scholar search platforms. We selected the studies that included the recurrence and/or progression rates or complete response rate in patients diagnosed with NMIBC according to their treatment and included MMC applied with EMDA. The last search was performed in November 2021.
RESULTS
The search yielded 64 articles; 11 articles met the selection criteria. In two of the 11 selected articles, mitomycin C was applied with an EMDA device (MMC-EMDA) as an ablative treatment, avoiding surgery in 50% of the patients. In 1 of the 11 studies, the application of MMC-EMDA was used as an induction treatment using a single preoperative instillation with promising results. In the remaining 8 studies, adjuvant MMC was applied with the EMDA device; in 3 of these 8 cases, treatment with MMC-EMDA alone was applied initially. In another3 cases the same treatment was applied after nonresponse to bacillus Calmette Guerin (BCG), and in the last 2 studies, MMC-EMDA was applied in combination with the classic therapy (BCG). All the studies selected supported the efficacy and safety of MMC-EMDA in patients with intermediate and high- risk bladder cancer. In 3 studies, adjuvant therapy with MMC-EMDA was performed in nonresponders to BCG, finding that adjuvant therapy with MMC-EMDA applied to BCG nonresponders without CIS avoided or delayed surgery.
CONCLUSIONS
The application of EMDA-enhanced MMC has been studied at different times of disease and with different administration protocols. It appears to delay bladder tumor recurrence and progression in certain populations. However, the methodological limitations of the published studies prevent definitive conclusions about its efficacy.
Topics: Humans; Mitomycin; Antibiotics, Antineoplastic; BCG Vaccine; Non-Muscle Invasive Bladder Neoplasms; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Administration, Intravesical; Neoplasm Invasiveness
PubMed: 36328923
DOI: 10.1016/j.urolonc.2022.09.016 -
PloS One 2021Urethral stricture disease is a common problem amongst men in Western countries often leading to a decreased quality of life. Current endoscopic treatment procedure...
BACKGROUND
Urethral stricture disease is a common problem amongst men in Western countries often leading to a decreased quality of life. Current endoscopic treatment procedure shows an unsatisfying stricture recurrence rate which could be improved by addition of local therapies.
OBJECTIVES
To provide an overview of both preclinical and clinical studies in order to investigate current level of evidence on the addition of local therapy to improve urethral stricture recurrence rates after endoscopic procedures.
METHODS
We performed a literature search in December 2020 and August 2021 using Cochrane, Embase, PubMed, Scopus and Web of Science and identified articles through combinations of search terms for 'urethral stricture disease', 'stricture formation' and 'local interventions'. We used the SYRCLE, RoB-2 and ROBINS-I tools to assess risk of bias across included studies. We did not perform a meta-analysis due to methodological differences between studies.
RESULTS
We included 32 articles in the qualitative analysis, 20 of which were preclinical studies and 12 clinical studies. Regarding preclinical articles using an animal model, nearly all interventions showed to have a positive effect on either urethral fibrosis, urethral stricture formation and/or fibrotic protein expression levels. Here, immunosuppressants and chemotherapeutics seemed most promising for possible clinical purposes. Regarding clinical studies, mitomycin-C and hyaluronic acid and carboxymethylcellulose showed positive effects on urethral stricture recurrence rates with low to intermediate risk of bias across studies. However, the positive clinical effects of mitomycin-C and steroids seemed to decrease in studies with a longer follow-up time.
CONCLUSION
Although local adjuvant use of mitomycin-C or hyaluronic acid and carboxymethylcellulose may carry clinical potential to improve urethral structure recurrence rates after endoscopic procedures, we believe that a large, well-designed RCT with a yearlong follow-up time is necessary to identify the true clinical value.
Topics: Animals; Extracellular Matrix; Humans; Publication Bias; Risk; Urethral Stricture
PubMed: 34614033
DOI: 10.1371/journal.pone.0258256 -
The Cochrane Database of Systematic... Aug 2021Trabeculectomy is a surgical treatment for glaucoma to lower intraocular pressure with high success rates; however, it is often associated with an increased rate of... (Review)
Review
BACKGROUND
Trabeculectomy is a surgical treatment for glaucoma to lower intraocular pressure with high success rates; however, it is often associated with an increased rate of cataract formation. Cataract can cause symptoms such as glare in bright conditions, foggy vision, and difficulty in driving at night. Cataract extraction surgery is highly successful in improving vision, but it comes at a cost of trabeculectomy failure, with a reported risk of 30% to 40%. An additional intervention to promote trabeculectomy survival after cataract extraction is needed. This review encompassed all adjunctive therapies used at the time of cataract surgery to increase trabeculectomy survival rate.
OBJECTIVES
To investigate the effect of the adjunctive modulation of wound healing during cataract surgery on the survival of a previously functioning trabeculectomy.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov; and the WHO ICTRP. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 April 2021.
SELECTION CRITERIA
We planned to include all randomised controlled trials (RCTs) of participants who had a functioning trabeculectomy and were undergoing cataract surgery that compared any adjunctive therapy intended to modulate wound healing (such as 5-fluorouracil, mitomycin C, or anti-vascular endothelial growth factor (VEGF) therapy) with no adjuvant therapy. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Our primary outcome was trabeculectomy failure at 6 months and 12 months after cataract surgery. Secondary outcomes were mean intraocular pressure difference from pre-cataract surgery baseline to 6 to 18 months post-cataract surgery; number of medications required to control eye pressure compared to before cataract surgery; bleb appearance as measured by a summation score of the Moorfields bleb grading system or other equivalent numerical grading systems; visual field progression measured by difference in mean deviation from baseline; and any complications.
MAIN RESULTS
We did not identify any RCTs of adjunctive modulation of wound healing during cataract surgery to promote survival of a previous trabeculectomy.
AUTHORS' CONCLUSIONS
There is a need for an RCT to investigate the role of adjuvant wound modulating therapy at the time of cataract surgery to promote survival of a functioning trabeculectomy.
Topics: Cataract; Cataract Extraction; Glaucoma; Humans; Trabeculectomy; Wound Healing
PubMed: 34355804
DOI: 10.1002/14651858.CD013664.pub2 -
BMC Cancer Nov 2019Chemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. This study reviewed and updated all published and eligible randomized controlled trials (RCTs) to compare the efficacy, prognosis, and toxicity of triplet chemotherapy with doublet chemotherapy in patients with advanced gastric cancer.
METHODS
RCTs on first-line chemotherapy in advanced gastric cancer on PubMed, Embase, and the Cochrane Register of Controlled Trials and all abstracts from the annual meetings of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology conferences up to October 2018 were searched. The primary outcome was overall survival, while the secondary outcomes were progression-free survival (PFS), time to progress (TTP), objective response rate (ORR), and toxicity.
RESULTS
Our analysis included 23 RCTs involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median OS (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and PFS (HR = 0.82; 95% CI, 0.69-0.97; P = 0.02) and TTP (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and ORR (OR = 1.21; 95% CI, 1.12-1.31; P < 0.0001) among overall populations. Compared with doublet chemotherapy, subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66-0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69-0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42-1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47-1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81-1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82-1.24; P = 0.94) chemotherapies. For different patients, compared with doublet chemotherapy, triplet chemotherapy improved OS (HR = 0.89; 95% CI, 0.81-0.99; P = 0.03) among Western patients but did not improve (HR = 0.96; 95% CI, 0.86-1.07; P = 0.47) that among Asian patients.
CONCLUSIONS
Compared with doublet chemotherapy, triplet chemotherapy improved OS, PFS, TTP, and ORR in patients with advanced gastric cancer in the population overall, and improved OS in Western but not in Asian patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Publication Bias; Retreatment; Stomach Neoplasms; Treatment Outcome
PubMed: 31747911
DOI: 10.1186/s12885-019-6294-9 -
Journal of Clinical Medicine Jul 2019The aim of this study was to determine the prophylactic effect of intravesical chemotherapy. Furthermore, it aimed to compare the efficacy of regimens on the prevention... (Review)
Review
The aim of this study was to determine the prophylactic effect of intravesical chemotherapy. Furthermore, it aimed to compare the efficacy of regimens on the prevention of bladder recurrence, after nephroureterectomy, for upper tract urothelial carcinoma by systematic review and network meta-analysis. A comprehensive literature search was conducted to search for studies published before 22 December 2016 using PubMed, Embase, and Scopus. All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The primary outcome was intravesical recurrence-free survival rate. In addition, we conducted indirect comparisons among regimens using network meta-analysis, as well as three randomized controlled trials (RCTs) on multicenter setting, and one large retrospective study with a total of 532 patients were analyzed. The pooled hazard ratio (HR) of bladder recurrence was 0.54 (95% CI: 0.38-0.76) in intravesical instillation patients. On network meta-analysis, pirarubicin was ranked the most effective regimen, while maintenance therapy of mitomycin C (MMC) with Ara-C and induction therapy of MMC were ranked as the second and third most effective regimens, respectively. Our study demonstrates that intravesical chemotherapy can prevent bladder recurrence in patients with upper tract urothelial carcinoma after nephroureterectomy. It also suggests that a single instillation of pirarubicin is the most efficacious intravesical regimen.
PubMed: 31331003
DOI: 10.3390/jcm8071059 -
Frontiers in Oncology 2023With the shortage of bacillus Calmette-Guérin (BCG) vaccine, it is important to find an alternative to BCG instillation, which is the most commonly used adjuvant...
Hyperthermia intravesical chemotherapy acts as a promising alternative to bacillus Calmette-Guérin instillation in non-muscle-invasive bladder cancer: a network meta-analysis.
INTRODUCTION
With the shortage of bacillus Calmette-Guérin (BCG) vaccine, it is important to find an alternative to BCG instillation, which is the most commonly used adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC) patients after transurethral resection of bladder tumor treatment (TURBt) to delay tumor recurrence. Hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C (MMC) is a potential treatment choice. We aim to compare HIVEC with BCG instillation for the preventive efficacy of bladder tumor recurrence and progression.
METHODS
A network meta-analysis (NMA) was taken with MMC instillation and TURBt as the attached comparators. Randomized controlled trials (RCTs) with NIMBC patients after TURBt were included. Articles with pure BCG unresponsive patients and combined therapies were excluded. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023390363).
RESULTS
It was found that HIVEC had a non-significant 22% relative reduction in bladder tumor recurrence compared with BCG instillation [HIVEC vs. BCG: HR 0.78, 95% credible interval (CrI) 0.55-1.08] and a nonsignificant higher risk of bladder tumor progression (BCG vs. HIVEC: HR 0.77, 95% CrI 0.22-3.03).
DISCUSSION
HIVEC is a potential alternative to BCG, and it is expected to be the standard therapy for NMIBC patients after TURBt during the global shortage of BCG.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier, CRD42023390363.
PubMed: 37251942
DOI: 10.3389/fonc.2023.1164932 -
Critical Reviews in Oncology/hematology Oct 2019The role of hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin in addition to cytoreductive surgery (CRS) has recently been questioned in peritoneal... (Comparative Study)
Comparative Study Meta-Analysis
Systematic review of published literature on oxaliplatin and mitomycin C as chemotherapeutic agents for hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases from colorectal cancer.
BACKGROUND
The role of hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin in addition to cytoreductive surgery (CRS) has recently been questioned in peritoneal metastases of colorectal cancer. Whether this applies to all published CRS/HIPEC regimens is unclear.
METHODS
A systematic literature search identified 46 studies on CRS/HIPEC using either oxaliplatin of mitomycin C with at least one oncological outcome parameter RESULTS: Oxaliplatin and mitomycin C studies were comparable regarding extent of disease, but differed substantially regarding synchronous versus metachronous presentation, application of neo-adjuvant systemic chemotherapy, duration of HIPEC, and completeness of cytoreduction for at least one of the oncological endpoints. Severe postoperative complication rate seemed significantly higher after oxaliplatin-based CRS/HIPEC.
CONCLUSION
Published cohorts on oxaliplatin-based CRS/HIPEC differed essentially from MMC-based procedures, especially considering the application of oxaliplatin-containing neo-adjuvant systemic therapy and shorter exposure time to intraperitoneal chemotherapy in oxaliplatin studies. No meaningful comparison could be made regarding DFS and OS.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Mitomycin; Oxaliplatin; Peritoneal Neoplasms
PubMed: 31400583
DOI: 10.1016/j.critrevonc.2019.06.014 -
The Journal of Surgical Research Jun 2024Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging... (Review)
Review
INTRODUCTION
Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance.
METHODS
Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization.
RESULTS
Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αβ-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance.
CONCLUSIONS
Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.
PubMed: 38851085
DOI: 10.1016/j.jss.2024.04.079 -
Clinical Otolaryngology : Official... Jul 2020Epiphora is a common clinical sign whose primary cause is post-canalicular lacrimal obstruction. Treatment is both surgical and non-surgical. In the literature, there is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epiphora is a common clinical sign whose primary cause is post-canalicular lacrimal obstruction. Treatment is both surgical and non-surgical. In the literature, there is some evidence to suggest that some treatments are superior to others, but there are no direct comparative data in this regard.
OBJECTIVE OF REVIEW
To analyse the success rates of all available treatments to resolve post-canalicular acquired lacrimal obstruction.
TYPE OF REVIEW
Systematic review and meta-analysis.
SEARCH STRATEGY
A literature search was conducted in the US National Library of Medicine (PubMed), EMBASE, SCOPUS and Cochrane databases with a final search performed in January 2020.
EVALUATION METHOD
The search strategy identified articles published later than 2000 with at least 50 procedures performed both surgically (external dacryocystorhinostomy [EXT-DCR], endoscopic dacryocystorhinostomy [END-DCR] and transcanalicular laser dacryocystorhinostomy [TCL-DCR]) and non-surgically (balloon dacryoplasty [DCP], probing-stenting [SP] and polyurethane stent [PoS]). The primary outcome was functional success, defined as symptom resolution or less than MUNK 2 scale; in addition to this, the influence of adjunctive treatments, such as application of mitomycin C and post-procedural silicone stenting, was evaluated.
RESULTS
In total, 14 958 papers were selected, 440 of which were reviewed after screening; 55 were included after full-text review, which involved 9337 procedures. Mean success rate was 48.9% (35.7%-62.3%) for DCP, 54.4% (41.8%-66.5%) for SP, 73.6% (59.7%-84%) for PoS, 80% (75.1%-84%) for TCL-DCR, 89.8% (83.3%-93.9%) for EXT-DCR and 89.5% (87.2%-91.5%) for END-DCR. Among all procedures, a difference was noted between DCP and END-DCR (P < .001), DCP and EXT-DCR (P < .001), SP and END-DCR (P < .001), SP and EXT-DCR (P < .001), END-DCR and PoS (P = .016), and END-DCR and TCL-DCR (P = .001); no differences were noted between END-DCR and EXT-DCR (P = 1.00), EXT-DCR and PoS (P = .121) and EXT-DCR and TCL-DCR (P = .223). Considering surgical procedures, no differences were seen if a silicone stenting was applied, whereas, due to heterogeneity of the literature data, no statistical analysis was feasible for application of mitomycin C.
CONCLUSIONS
Our analyses suggest that, among all procedures available, END-DCR and EXT-DCR should be considered as treatments of choice to resolve distal acquired lacrimal obstruction.
Topics: Alkylating Agents; Dacryocystorhinostomy; Endoscopy; Humans; Lacrimal Duct Obstruction; Mitomycin; Stents
PubMed: 32304619
DOI: 10.1111/coa.13551